PB1831: UTILITY OF FLT3 INHIBITORS IN PATIENTS WITH ACUTE MYELOID LEUKEMIA (AML) AND T(6;9)(P22;Q34)
Authors: F. Ong, T. M. Kadia, N. J. Short, M. Yilmaz, Y. Alvarado, S. Pierce, G. Garcia-Manero, C. DiNardo, G. Borthakur, M. Konopleva, N. Daver, H. Kantarjian, F. Ravandi
Journal: HemaSphere (2022)

Background: Efficacy of FLT3 inhibitors in patients (pts) with AML and t(6;9)(p22;q34)/DEK-NUP214 is not well established. Aims: We compared overall survival (OS) and event-free survival (EFS) of AML pts with t(6;9) who received FLT3 inhibitor (FLT3-i) in frontline (FL) or salvage (SL) setting, regardless of their FLT3 mutation status. Methods: We retrospectively evaluated pts with AML or high-risk Myelodysplastic Syndrome (HR-MDS) who presented to our center between 1995-2021. Among 9936 pts, 55 pts (0.5%) had t(6;9) (48 AML, 7 HR-MDS). In FL setting, pts were divided according to their induction regimen with (n:5) or without FLT3-i (n:48). In SL setting, 35 pts who relapsed or were refractory to FL regimen were recategorized according to their SL regimen with (n:16) or without FLT3-i (n:17). Four pts were excluded from analysis due to incomplete data. Results: Among 47 pts with available molecular data, 35 (74%) was FLT3-ITD+, 5 (10.6%) with both ITD and TKD mutation. ITD allelic ratio (AR) was known for 28 (80%) pts (AR range: 0.01-0.95) with 11 (31%) pts having an AR ≥0.5. Age was well-balanced across all cohorts with median of 41 years (yr). Most pts had ECOG performance status of 0-1 (92%) on presentation. Pts with FLT3-ITD mutation were more likely (83%) to receive intensive chemotherapy (IC) compared to pts without (50%, p=0.02). Most pt in FL cohort with or without FLT3-i received IC (80% and 77%, respectively). There was no significant different in FLT3-ITD positivity between FL cohort with or without FLT3-i (p=0.3). Sorafenib was used in 62% of cases, followed by Quizartinib (24%). All pts in FL cohort with FLT3-i achieved CR/CRi with 60% MRD negative rate as compared to 52% in non-FLT3-I, and 60% of FLT3-i cohort had stem cell transplantation (SCT) in CR1 (vs. 21% of non-FLT3-i). Median number (No.) of therapy cycle was 1 to reach CR/CRi in all FL cohorts. Outcomes are shown in Figure 1. With median follow up of 47 months (mos), 2-yr OS and EFS were higher in FLT3-i than non-FLT3-i cohort (80% and 60% vs. 41% and 20%, respectively), although not statistically significant (p=0.2 for OS and 0.1 for EFS). Among pts with known mutation status, there were non-significant lower 2-yr OS and EFS in FLT3-ITD+ pts than wild-type FLT3 (FLT3-wt) pts (44% and 22% vs. 58% and 42%, respectively; p=0.4 for OS and 0.3 for EFS), regardless of whether FLT3-i was included in the induction regimen. CR/CRi rate was similar between FLT3-ITD+ (57%) and FLT3-wt pts (58%) but FLT3-wt pts was more likely to receive SCT in CR1 (42%) than FLT3-ITD+ pts (23%). In SL setting, 75% pts in FLT3-i cohort received low intensity therapy as compared to 12% pts in non-FLT3-i cohort (p<0.01) and 69% pts in SL cohort without FLT3-i were FLT3-ITD+ (p=0.03). Pts were heavily treated in both group (67% pts were in salvage 2+), but never received FLT3-i as part of their prior salvage regimen. No. of prior therapies and proportion of pts with prior SCT and FLT-i- containing induction regimen were similar across cohort. CR/CRi rate was higher in FLT3-i cohort (69%) than non-FLT3-i cohort (41%) after median No. of 1 therapy cycle with similar proportion of pts who went to SCT post salvage regimen. With median follow up of 47 mos, 2-yr OS and EFS were poor in both FLT3-i cohort and non-FLT3-i cohort (27% and 12% vs. 12.5% and 6%, respectively, p=0.3 for OS and 0.7 for EFS). Image:Summary/Conclusion:FLT3 mutation status does not impact survival in pts with t(6;9). Addition of FLT3-i to FL and SL regimen in subset of pts with FLT3-ITD mutation is beneficial and should be further evaluated.